Design of a new structure of immunogenic chimeric polytope against human various cancers using immunoinformatics and structural methods

Abstract

Cancer is one of the deadliest diseases in recent decades. Which has different types.Despite advances in the treatment of cancer, they are still the most critical threat topublic health. Although conventional therapies have played a major role in the treat-ment or eradication of the disease, the emergence of emerging diseases requires newtherapies such as vaccine design. Significant challenges in cancer drug treatment suchas drug resistance and side effects of drug toxicity and high cost have made the treat-ment process more difficult. The aim of this study was to design a new and effectivestrategy for preparing a vaccine against cancer using some antigenic proteins in thisdisease. After preparing appropriate epitopes of antigenic protein compounds in can-cers and examining their antigenic and immunogenic properties, the process of fusionvaccine composition was performed with the help of various bioinformatics tools tostudy the physicochemical properties and two-dimensional and three-dimensionalstructures and Their validation as well as immunological and simulation propertieswere investigated and finally the codons of vaccine constructs were optimized to in-crease the translation rate of its cloning process in the expression vector pET28a (+)to evaluate the expression of protein in prokaryotic cells in E. coli K12 system. Finally,the docking process was performed with some receptors that are effective in immuno-logical processes in the body, such as TLRs, MHCI, and MHCII. Selected epitopes ofphysiologically important cancer proteins theoretically cover a high percentage of theworld’s population. The vaccine was designed with a stable, antigenic, and non-sen-sitizing composition. Structural analysis of the TRL5/vaccine binding complex andits simulation process reveal sufficiently stable critical with the prospect of receptorrecognition. The dynamics of the immune response, having the potential to stimulateand produce active and memory B cells, and the production of CD8+T, and CD4+Tcells show a favorable role in stimulating and creating effective immune responses byTh2 and Th1 cells. Computational results using bioinformatics tools showed that ourdesigned immunogenic structure has the potential to stimulate cellular and humoralimmune responses against cancer properly. Therefore, based on these data and afterevaluating the effectiveness of the candidate vaccine through in vivo and in vitro im-munological tests, it can be suggested as a candidate vaccine against cancer.